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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
23 March 2010 - 06 April 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study has been performed according to OECD and EC guidelines and according to GLP principles. For justification of read-across see CSR chapter 1.3.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Diammonium hydrogenorthophosphate
- Substance type: White crystals
- Physical state: Solid.
- Analytical purity: 99.8%
- Purity test date:19-09-2008
- Lot/batch No.: 0907099
- Expiration date of the lot/batch: 03 February 2011 (allocated by NOTOX, 1 year after receipt of the test substance)
- Stability under test conditions:Stable under storage conditions.
- Storage condition of test material: At room temperature in the dark
- Other:
Hygroscopic: Yes, store in well-sealed container
pH: 8.1 (1M)

Test animals

Species:
rat
Strain:
other: Crl:WI(Han)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals were selected (approximately 10 weeks old).
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: No.
- Housing:
Before exposure:
Group housing of five animals per sex per cage in labeled Macrolon cages (type IV; height 18 cm) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
After exposure:
Group housing as described above, except that a paper sheet was introduced into the cage covering the bedding and cage enrichment to prevent suffocation in case of bad health condition. At the end of the day of exposure the paper sheet was removed.
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) except during exposure to the test substance.
- Water (e.g. ad libitum): Free access to tap water except during exposure to the test substance.
- Acclimation period: At least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8-21.7 °C
- Humidity (%): 42-60%
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 23 March 2010 To: 06 April 2010

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle).
Details on inhalation exposure:
Animals were exposed to the test substance via the inhalatory route. For this purpose the animals were placed in restraining tubes, connected to the exposure chamber.
The design of the exposure chamber was based on the flow past nose-only inhalation chamber (Am. Ind. Hyg Assoc. J. 44(12): 923-928, 1983). The chamber consisted of 3 animal sections with 8 animal ports each. The number of animal sections and number of open animal ports were adapted to the air flow in such a way that at each animal port the theoretical air flow was on average 1.4 L/min, which ensures an adequate oxygen supply to the test animals. The inlet of the test atmosphere was located at the top section and the outlet was located at the bottom section. The direction of the flow of the test atmosphere guaranteed a freshly generated atmosphere for each individual animal.
The placement of the individual animals in the inhalation chamber is shown in the test report. All components of the exposure chamber, which could come in contact with the test material, were made of stainless steel, glass, rubber or plastic. To avoid exposure of the personnel and contamination of the laboratory the exposure chamber was placed in a fume hood, which was maintained at a slightly negative pressure.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
5.5 mg/L
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
Diammonium hydrogenorthophosphate was administered as an aerosol by inhalation for a single but interrupted exposure lasting 4 hours and 8 minutes in total to one group of three male and three female Wistar rats. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 mg/L air
Exp. duration:
4 h
Mortality:
No mortality occurred and no clinical signs were noted during the study.
Clinical signs:
During and after exposure no clinical signs were noted.
Body weight:
Overall body weight gain in males and females were within the range expected for rats of this strain and age used in this type of study.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The inhalatory LC50, 4h value of Diammonium hydrogenorthophosphate in Wistar rats was considered to exceed 5 mg/L under the conditions in this study.
Executive summary:

Assessment of acute inhalatory toxicity with Diammonium hydrogenorthophosphate in the rat

 

The study was carried out based on the guidelines described in:

- OECD Guidelines, Section 4, Health Effects. No.403, "Acute Inhalation Toxicity", September 2009.

- Commission Regulation (EC) No 440/2008,B.2. Acute Toxicity (inhalation),L142, May 2008.

- EPA OPPTS 870.1300, Acute inhalation Toxicity. EPA 712-C-98-193, August 1998.

- JMAFF, 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.

 

Diammonium hydrogenorthophosphate was administered as an aerosol by inhalation for 4 hours to one group of five male and five female Wistar rats. Animals were subjected to daily observations and determination of body weight on Days 1, 2, 4, 8 and 15. Macroscopic examination was performed after terminal sacrifice (day 15).

 

The mean actual time-weighed concentration was 4.84 ± 0.28 mg/L. The nominal concentration was 442.92 mg/L. The generation efficiency (ratio of actual and nominal concentration) was 1.1%.

 

The Mass Median Aerodynamic Diameter (MMAD) and geometric standard deviation (gsd) were determined twice. The MMAD was 6.0mm and 5.6mm respectively and the gsd was 1.8 in both cases.

 

No mortality occurred and no clinical signs were noted during and after exposure.

 

The body weight gain shown by the animals over the study period was considered to be normal.

 

No abnormalities were found at macroscopic post mortem examination of the animals.

 

Agglomeration of aerosol particles at this high concentration tested resulted in MMAD values to exceed the recommended range of 1 - 4 µm. Additional efforts to reduce the MMAD were unsuccessful and the MMAD remained significantly larger than 4 µm (i.e. use of a micronizing jet-mill and two cyclones, lowering the concentration down to 1 mg/L). Since the gsd of 1.8 determined during the actual exposure indicated that the aerosol was polydisperse and since approximately 20% of the particles were smaller than 4 µm, it can be assumed that test substance deposition in the lower respiratory tract occurred during the exposure.

 

It was therefore considered that the outcome of this study is valid for the limit concentration of 5 mg/L.Since no mortality occurred at the limit concentration, no full study using lower concentrations was conducted.

 

The inhalatory LC50, 4hvalue of Diammonium hydrogenorthophosphate in Wistar rats was considered to exceed 5 mg/L under the conditions in this study.

 

Based on these results Diammonium hydrogenorthophosphate does not have to be classified and has no obligatory labelling requirement for acute inhalation toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.